The molecular mechanisms determining rates of degradation of specific proteins and mRNAs in mammalian cells will be analyzed. The research will focus on comparison of mechanism of degradation of two proteins in rat liver and cultured hepatoma cells, one very labile (tyrosine aminotransferase, t1/2 equals 1.5 hr) and the other stable (alanine aminotransferase, t1/2 equals 3 days) as well as on their cognate mRNAs which exhibit comparable differences in intracellular stability. Specific factors thought to be acting in tyrosine aminotransferase turnover will be sought. The enzymes will be purified and their stabilities determined under a variety of experimental conditions to relate structure to intracellular turnover. The mRNAs will be purified and the relationship of their structures to intracellular stability determined. Products of degradation of both the proteins and the mRNAs will be characterized. The objective is to determine how the intracellular degradative mechanisms operate to control cellular phenotype in normal and abnormal cells.